Mass spectrometry is an indispensable technique for the analysis of biologically important compounds. Thus, the development of techniques for mass spectrometric analysis of large, labile, polar molecules is of great importance to progress in the biomedical, biochemical, and biological sciences. It is our general objective to extend the utility of organic mass spectrometry in biomedicine and biochemistry. Our specific aims are as follow: 1. experimentally investigate the physical and chemical processes which govern the ejection of secondary ions from solid and liquid matrices during bombardment with keV particles; 2. formulate and test mechanistic hypotheses for deposition and partitioning of energy into organic sample matrices and for fragmentation and ionization of sputtered molecules; 3. utilize knowledge of the fundamental processes to optimize source designs and experimental protocols for secondary ion mass spectrometry of high molecular weight, labile, polar molecules of biochemical and biological interest. The liquid metal ion primary source is the key to achieving our experimental aims. We have pioneered the use of this unique and versatile ion source in secondary ion mass spectrometry (SIMS). The usefulness of mass spectrometry is reduced when important biomolecules cannot be analyzed due to limitations on mass range, sensitivity or compound types. Relatively recently, SIMS employing either atomic ion or neutral atom primary beams and liquid sample matrices has contributed significantly to removing numerous restrictions on the mass spectrometric analysis of thermally labile, high molecular weight, organic compounds. It is our premise that research which leads to enhancement of the capabilities of molecular SIMS will have made a major contribution toward applying mass spectrometry to important problems in biomedicine and biochemistry. This, then, is how our specific aims are related to our long-stranding general objective.